Phenotypic changes of γδ T cells in Plasmodium falciparum placental malaria and pregnancy outcomes in women at delivery in Cameroon.

Introduction: Depending on the microenvironment, γδ T cells may assume characteristics similar to those of Th1, Th2, Th17, regulatory T cells or antigen presenting cells. Despite the wide documentation of the effect of Th1/Th2 balance on pregnancy associated malaria and outcomes, there are no reports on the relationship between γδ T cell phenotype change and Placental Malaria (PM) with pregnancy outcomes. This study sought to investigate the involvement of γδ T cells and its subsets in placental Plasmodium falciparum malaria. Methods: In a case-control study conducted in Yaoundé, Cameroon from March 2022 to May 2023, peripheral, placental and cord blood samples were collected from 50 women at delivery (29 PM negative: PM- and 21 PM positive: PM+; as diagnosed by light microscopy). Hemoglobin levels were measured using hemoglobinometer. PBMCs, IVBMCs and CBMCs were isolated using histopaque-1077 and used to characterize total γδ T cell populations and subsets (Vδ1+, Vδ2+, Vδ1-Vδ2-) by flow cytometry. Results: Placental Plasmodium falciparum infection was associated with significant increase in the frequency of total γδ T cells in IVBMC and of the Vδ1+ subset in PBMC and IVBMC, but decreased frequency of the Vδ2+ subset in PBMC and IVBMC. The expression of the activation marker: HLA-DR, and the exhaustion markers (PD1 and TIM3) within total γδ T cells and subsets were significantly up-regulated in PM+ compared to PM- group. The frequency of total γδ T cells in IVBMC, TIM-3 expression within total γδ T cells and subsets in IVBMC, as well as HLA-DR expression within total γδ T cells and Vδ2+ subset in IVBMC were negatively associated with maternal hemoglobin levels. Furthermore, the frequency of total γδ T cells in PBMC and PD1 expression within the Vδ2+ subset in CBMC were negatively associated with birth weight contrary to the frequency of Vδ1-Vδ2- subset in PBMC and HLA-DR expression within the Vδ2+ subset in IVBMC which positively associated with maternal hemoglobin level and birth weight, respectively. Conclusion: The data indicate up-regulation of activated and exhausted γδ T cells in Plasmodium falciparum placental malaria, with effects on pregnancy outcomes including maternal hemoglobin level and birth weight.

Chemokine modulation in microscopic and submicroscopic Plasmodium falciparum malaria infection in women at delivery in Yaoundé, Cameroon.

In pregnancy-associated malaria, chemokines such as CXCL-4, CXCL-13, CXCL-16, and CCL-24 play critical roles in leucocyte trafficking to tissue sites in the infected placenta where inflammatory reactions are active. However, how plasma levels of these chemokines associate with Plasmodium falciparum placental malaria and pregnancy outcomes remains not well understood. The present study analyzed the plasma levels of CXCL-4, CXCL-13, CXCL-16, and CCL-24 chemokines in matched peripheral, placental and cord blood in relation with placental malaria (PM), and with submicroscopic parasitaemia. This was a retrospective case-control study (1:3 ratio) involving samples from 134 women (34 PM+ and 100 PM-) enrolled at delivery at the Marie Reine Health Center in Yaoundé, Cameroon between June 2013 and October 2018. Samples were collected just after delivery and used to diagnose microscopic and submicroscopic Plasmodium falciparum infections. Submicroscopic infections were detected by reverse transcription LAMP whereas chemokine levels were determined by Magnetic Luminex Screening Assay. Overall, PM was associated with increased plasma levels of CXCL-13 and CXCL-16 and low levels of CXCL-4 and CCL-24 in both peripheral and placental blood (0.0002 ≤ p ≤ 0.042). Similarly, CCL-24 levels in peripheral and placental blood samples were significantly lower in submicroscopically infected women compared to healthy controls (p = 0.04 and 0.02, respectively). Maternal hemoglobin levels increased with peripheral plasma levels of CXCL-4 (p = 0.005), CXCL-16 (p = 0.03), and CCL-24 (p = 0.002) while birth weight was lower for babies born from women with high levels of peripheral CXCL-13 (p = 0.0006) and low levels of cord CXCL-4 and CCL-24 (p = 0.02 and 0.08, respectively). Together the data suggest that low levels of CXCL-4 and CCL-24 coupled with high plasma levels of CXCL-13 and for a lesser extend CXCL-16 represent signatures of PM in the study population. These findings are relevant for understanding the immunopathogenesis of PM and developing new therapeutic or preventive strategies against severe PM outcomes.